title: Comparative evaluation of synergy of combinations of beta-lactams with fluoroquinolones or a macrolide in Streptococcus pneumoniae.
abstract: OBJECTIVE
  Streptococcus pneumoniae has shown a great ability to develop efficacious mechanisms of resistance to the main drugs for the treatment of pneumonia, such as β-lactams, macrolides and fluoroquinolones. The present study aimed to compare the antipneumococcal activity of combinations of respiratory fluoroquinolones with cephalosporins (either parenteral or oral) or protected penicillin versus the standard combinations (i.e. a macrolide with a protected penicillin or cephalosporin) against 100 isolates with different susceptibilities to macrolides and/or penicillin.
  
  
  METHODS
  Chequerboard assays for all isolates and time-kill curves for nine isolates with different patterns of susceptibility were performed. Synergy between antibiotics at serum peak concentrations was also determined.
  
  
  RESULTS
  The combination of levofloxacin with ceftriaxone produced the highest rate of synergy (54/100), mainly against macrolide-resistant strains (22/30). Antagonism was not observed for any tested combination apart from clarithromycin with amoxicillin/clavulanic acid (22/100 isolates). Although the killing activities of all antibiotics improved when they were tested in combination, synergy was observed only for some combinations after 12 and/or 24 h. Serum concentrations were effective in inhibiting the growth of the tested strains.
  
  
  CONCLUSIONS
  Combinations of levofloxacin with parenteral cephalosporins were the most active among all the tested combinations, while antagonism occurred when clarithromycin and amoxicillin/clavulanic acid were tested.
authors.affiliation: Laboratory of Clinical Chemistry and Microbiology, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy. lorenzo.drago@unimi.it
authors.forename: L
authors.initials: L
authors.lastname: Drago
authors.forename: L
authors.initials: L
authors.lastname: Nicola
authors.forename: V
authors.initials: V
authors.lastname: Rodighiero
authors.forename: M
authors.initials: M
authors.lastname: Larosa
authors.forename: R
authors.initials: R
authors.lastname: Mattina
authors.forename: E
authors.initials: E
authors.lastname: De Vecchi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004347:Drug Interactions; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011008:Pneumococcal Infections / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D013997:Time Factors; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D018942:Macrolides; D047090:beta-Lactams